SKELETAL BIOLOGY AND ARTHRITIS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 该提案利用转基因小鼠模型来探索非炎性关节变性（骨关节炎）的生物学机制。虽然晚期炎症事件已被更彻底地研究，但骨关节炎关节退行性变的最初原因尚不清楚。骨关节炎的一些原因可能存在于复杂的调控网络中，该网络在生命早期协调骨骼的发育和生长事件。利用新获得的信息，胶原蛋白类型Xi和新开发的转基因小鼠系，我们将描述Col 11 a1 DVR小鼠，这可能会揭示一个新的水平的理解骨关节炎的骨骼发育和疾病进展。改善骨关节炎的诊断和治疗可能会导致更彻底地了解导致早期骨关节炎发展的因素，例如调节纤维形成或协调骨软骨替代的因素。有证据表明，Col 11 a1在这些过程中是必不可少的。这些研究可以让我们深入了解未来预防和治疗策略的目标。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This proposal utilizes a genetically modified mouse model to explore the biological mechanisms underlying non-inflammatory joint degeneration (osteoarthritis). Although late-stage inflammatory events have been more thoroughly investigated, the initial causes of joint degeneration in osteoarthritis are unknown. Some of the causes of osteoarthritis may lie within the complex regulatory networks that orchestrate the events of development and growth of the skeleton early in life. Utilizing newly acquired information about collagen type XI and a newly developed genetically modified mouse line, we will characterize the Col11a1DVR mouse, which may reveal a new level of understanding of skeletal development and disease progression in osteoarthritis. Improved diagnosis and treatment of osteoarthritis will likely result from a more thorough understanding of factors that lead to a predisposition for the development of osteoarthritis early in life, such as those that regulate fibrillogenesis or coordinate the replacement of cartilage by bone. Evidence suggests that Col11a1 is essential in these processes. These studies may give us insight into targets for future preventive and therapeutic strategies.